Perinatal opioid exposure alters alcohol-driven reward behaviors in adolescent male and female rats.

Differential effects of gestational arsenic exposure on the liver and kidney of rat offspring across postnatal development.

ABSTRACTBackgroundGestational diabetes mellitus (GDM), a common pregnancy complication characterized by maternal hyperglycemia, negatively impacts offspring health. Skeletal muscle, a critical tissue for glucose and lipid metabolism, is especially vulnerable to prenatal environmental insults. However, the effects of intrauterine hyperglycemia (IUHG) on offspring skeletal muscle development remain poorly understood. This study aimed to investigate the effects of IUHG on skeletal muscle development in offspring and evaluate whether postnatal exercise could mitigate these effects.MethodsPregnant mice were assigned to GDM and control groups. Offspring were further divided into control and exercise subgroups. Body weight, glucose tolerance test (GTT), insulin tolerance test (ITT), body composition, muscle strength and exercise capacity were assessed. At 20 weeks of age, skeletal muscle morphology was evaluated via various staining and Transmission Electron Microscope. Transcriptomic changes were analysed by RNA sequencing (RNA‐seq) and chromatin accessibility was assessed using ATAC‐seq to identify molecular mechanisms underlying IUHG‐induced alterations. Additionally, primary fetal myoblasts were cultured under normal and high‐glucose conditions to investigate metabolic changes and lipid accumulation in vitro.ResultsOffspring exposed to IUHG exhibited increased body weight, impaired glucose and insulin tolerance, altered body composition, reduced muscle strength and diminished exercise capacity at adulthood. Exercise intervention in diabetic offspring improved the muscle ratio (p < 0.05), fat ratio (p < 0.05), lipid profiles (p < 0.005) and muscle structure and strength (p < 0.005). Transcriptomic and epigenomic profiling identified significant changes in genes and regulatory elements associated with immune regulation, myogenesis, lipid metabolism and inflammation in GDM‐exposed offspring. In vitro, high‐glucose exposure of E14.5d fetal myoblasts led to significant metabolic reprogramming, including lipid accumulation and disruptions in glycolysis and oxidative metabolism. Furthermore, the expression of AP‐1 family members Fos and Junb was up‐regulated in myoblasts under high‐glucose conditions, which aligns with the findings in the in vivo models.ConclusionsIUHG disrupts skeletal muscle development and metabolic function in offspring through structural, transcriptional and epigenetic alterations. Postnatal exercise partially reversed these impairments, highlighting its potential as a non‐pharmacological intervention. These findings provide new insights into the developmental origins of skeletal muscle dysfunction in GDM‐exposed offspring and underscore the importance of early prevention strategies.

Background: The effect of intrauterine exposure to SARS-CoV-2 infection during pregnancy on neurodevelopment and growth trajectories during the first year of life remains under investigation. Methods: We retrospectively reviewed the electronic medical records of all pregnant women who received care at Mayo Health System and tested positive for SARS-CoV-2 (RT-PCR) from March 2020 through October 2021 and examined the effects of fetal sex and trimester of maternal SARS-CoV-2 infection on the risk of neurodevelopmental disorder diagnosis and growth trajectories of head circumference (HC) and body weight (BW) percentiles over the first year of life using linear mixed models. Results: We observed that a higher percentage of male infants (n = 357), compared to females (n = 344), have neurodevelopmental disorders (10.9% vs. 5.2%, p = 0.008), and infants exposed to maternal SARS-CoV-2 infection in the second (n = 183) or third trimester (n = 358) have a higher prevalence of neurological diagnoses compared to those exposed in the first trimester (n = 160) (1st vs. 2nd vs. 3rd trimester: 0% vs. 0.9% vs. 0.7%, respectively, p = 0.037). In addition, female infants, compared to males, had significantly lower BW (B = −0.04, p < 0.0001) and HC (B = −0.06, p < 0.0001) percentile growth trajectories over the first year of life. Moreover, infants exposed to maternal SARS-CoV-2 infection in the second trimester had a significantly lower BW percentile growth trajectory (B = −0.01, p = 0.006), while infants exposed to maternal SARS-CoV-2 infection in the third trimester had a significantly lower HC percentile growth trajectory (B = −0.02, p = 0.02). Conclusions: In utero exposure to maternal SARS-CoV-2 infection could have long-term effects on growth trajectories, depending on the infant’s sex and timing of exposure.

&lt;p&gt;Cardiovascular disease (CVD) remains the leading cause of global mortality, with a concerning trend toward younger onset. This shift highlights the urgent need to advance the window of attention and intervention for cardiovascular health (CVH). The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that adverse intrauterine exposures can program long-term alterations in offspring CVH, underscoring the significance of early-life origins. Maternal health conditions during pregnancy, environmental exposures, and lifestyle factors are consistently associated with adverse cardiovascular outcomes in children, including elevated blood pressure, structural and functional abnormalities, and impaired cardiometabolic profiles. These associations are mediated through pathways involving placental dysfunction, inflammation, oxidative stress, and hormonal imbalance, which collectively reshape fetal cardiovascular development and increase susceptibility to CVD later in life. From a management perspective, adverse intrauterine exposures should be integrated into pediatric CVH risk assessment, and preventive strategies should be shifted to the preconception and prenatal periods. This review highlights intrauterine environment as a critical determinant of intergenerational cardiovascular risk and emphasizes the necessity of implementing precision prevention strategies beginning from the earliest stages of life.&lt;/p&gt;

This study aimed to determine the effects of macro-environmental factors such as sex, birth type, parity, and birth weight on the hair cortisol concentrations of newborn Akkeçi goat kids. Hair samples were collected from 44 Akkeçi goat kids within the first 24 hours following birth and cortisol concentrations were quantified using an ELISA assay kit. Statistical analysis revealed that sex, birth type, parity, and birth weight had no significant effect on the hair cortisol concentrations (p&amp;gt;0.05). Although not statistically significant, male kids tended to exhibit higher cortisol levels than females; singleton kids showed higher levels than twins or triplets; and kids born to multiparous does had higher levels than those born to primiparous does. These findings suggest that hair cortisol collected at birth reflects intrauterine hormonal exposure but is not strongly influenced by macro-environmental factors. Overall, the hair matrix appears to be a useful indicator for assessing intrauterine hormonal exposure in newborn Akkeçi goat kids.

This study aimed to systematically characterize the features and drug distribution of neonatal adverse drug reactions using data from the FAERS, with a focus on exposure-specific patterns and stratified analyses by sex and clinical outcomes.Reports submitted to FAERS from the first quarter of 2004 to the fourth quarter of 2024 were utilized. Patients experienced the ADR at an age of no more than 28 days. Four quantitative disproportionality analysis methods, including ROR, PRR, BCPNN, and MGPS, were used to detect signals of adverse drug events.A total of 15,456 neonatal cases exposed to the target drugs were included, yielding 60,611 adverse event reports, 95.45% of which were classified as serious. The median time to onset of ADRs was 264 days for intrauterine drug exposure, compared to 1-3 days for extrauterine exposure. The most affected SOCs were injury and procedural complications (19.53%), congenital disorders (15.96%), and pregnancy/perinatal conditions (8.65%). Transplacental exposure accounted for the highest proportion (52.47%), followed by intravenous (9.34%), oral (6.77%), breastfeeding (1.80%), intramuscular (1.48%), and inhalation (1.29%). The top maternal exposure drugs included venlafaxine, sertraline, quetiapine, lamotrigine, and levetiracetam. For intravenous use, levetiracetam, zidovudine, indomethacin, ibuprofen, and vancomycin were most common. Female neonates had higher risks of microcephaly, ventricular septal defect, and growth restriction, while male neonates were more prone to hypospadias, cryptorchidism, and agitation. Serious AEs were mainly linked to maternal drug exposure during pregnancy.These results showed that the use of antidepressants, antiepileptics, and antivirals during pregnancy represents a significant risk factor for neonatal adverse reactions, particularly congenital malformations. Consequently, it is imperative to implement precise prevention strategies tailored to specific exposure stages and to advocate for the establishment of an international pharmacovigilance network for neonates.

In April 2025, the European Alliance of Associations for Rheumatology (EULAR) published recommendations on the use of antirheumatic drugs in the reproductive phase, during pregnancy and while breastfeeding. The previous EULAR Points to Consider from 2016 were updated and replaced. The task force formulated five overarching principles and twelve recommendations for the use of antirheumatic drugs before and during pregnancy, while breastfeeding and in male patients. The overarching principles emphasise the great importance of effective control of disease activity during pregnancy and breastfeeding to protect mother and child. In contrast to the 2016 version, biologics, especially tumour necrosis factor inhibitors, are considered safe both during pregnancy and breastfeeding. On the other hand, greater caution is recommended when using nonsteroidal anti-inflammatory drugs and glucocorticoids, especially in higher doses and over longer periods of time. New recommendations have been included for antirheumatic drugs and male fertility as well as for vaccinations in infants after intrauterine exposure to biologics. This "Hot Topic" summarises the EULAR recommendations for German rheumatologists.

Development of children at age 7-8years after intrauterine exposure to selective serotonin reuptake inhibitors (SSRIs) - Results from the Dutch prospective cohort SMOK study.

Gestational Diabetes Mellitus (GDM) is a glucose intolerance disorder that arises or is first diagnosed during pregnancy in women without a prior history of diabetes. With the global rise in obesity and type 2 diabetes, the prevalence of GDM continues to increase, posing serious threats to maternal and child health. Evidence shows that intrauterine exposure to maternal hyperglycemia can predispose offspring to obesity, glucose intolerance, and metabolic diseases later in life. This review summarizes the impact of GDM on offspring birth outcomes, growth trajectories during infancy and early childhood, explores the underlying biological mechanisms, and discusses research limitations and future perspectives.

The prevalence of maternal obesity is rapidly increasing, which represents a major public health concern worldwide. Currently more than 50% of all adult women are overweight or obese, and this trend is reflected in women of child-bearing age. Maternal obesity is characterized by metabolic dysfunction and chronic inflammation, and is associated with health problems in both the mother and the offspring. Intrauterine programming occurs during embryonic and fetal development, a critical period not only for the formation of tissues and organs but also for the etiology of diseases later in life. The principal mechanisms underlying fetal programming in the offspring of obese mothers appear to involve DNA methylation and chromatin remodeling within progenitor cells. Aberrant DNA methylation patterns have been identified in genes involved in insulin signaling, lipid metabolism, and appetite regulation in the placenta and fetal tissues. Histone modifications, such as acetylation and methylation of histone tails, may also play a crucial role in modulating chromatin structure and accessibility of transcriptional machinery to DNA. The persistence of such modifications throughout life, and potentially across generations, can lead to permanent alterations in gene expression, thereby contributing to the intergenerational transmission of metabolic disorders. The aim of this paper is to present an overview of the current knowledge regarding the effects of maternal obesity on fetal development and the occurrence of fetal complications, as well as long-term complications observed in adulthood related to intrauterine exposure to maternal obesity, including hypertension and cardiovascular diseases, impaired insulin secretion and resistance, diabetes mellitus, and metabolic syndrome. The mechanisms underlying fetal programming are also discussed.

Preeclampsia is a hypertensive disorder of pregnancy characterised by new onset hypertension at ≥ 20 weeks’ gestation accompanied by maternal organ dysfunction and/ or fetal compromise. This hypertensive exposure in pregnancy has known long-term consequences for both the mother and child. Presently, the mechanisms for these cardiometabolic, immunological and neurodevelopmental consequences in the child aren’t well characterised, but epigenetic changes in development and premature biological aging may play a role in the development of these long-term morbidities. To investigate, we assessed genome-wide DNA methylation and biological aging in the blood of 2–5 year-old children with (n = 20) or without (n = 20) previous intrauterine exposure to preeclampsia. Exposure to preeclampsia was associated with 103 differentially methylated regions (DMRs) proximal to both known and novel candidate genes. Biological aging, as determined by two telomere length quantification methods and an epigenetic clock, was found to not be statistically different between the preeclampsia exposure and normotensive pregnancy groups. From the 103 DMRs, gene ontology analysis highlighted that 17 regions are proximal to genes involved in cell–cell adhesion (p = 7.49 × 10–12), and more specifically homophilic cell adhesion (p = 7.49 × 10–12). This is the first study to consider genome-wide epigenetic changes in the blood of young children exposed to preeclampsia in utero, with previous studies concentrating on cord blood or placental biopsy material collected at birth.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13148-025-02029-1.

Multiple prenatal adverse environmental factors alter hepatic cytochrome P450 (CYP) enzymes expression in offspring, with these changes persisting after birth. These factors induce fetal exposure to excessive maternal glucocorticoids (GCs), however, the mechanisms by which intrauterine GCs exposure programs offspring CYP expression remain unclear. Given that GCs are high‐affinity ligands for the glucocorticoid receptor (GR), this work employs dexamethasone (DEX), a GR agonist, to establish a prenatal dexamethasone exposure (PDE) model for investigating the role of GR activation in CYPs programming. The model is implemented to pregnant Wistar rats and heterozygous liver‐specific GR knockout mice. Results show that PDE consistently increases the expression of hepatic CYP3A1 and CYP2B1, thereby enhancing the metabolic enzyme efficiency in adult male offspring. In vitro experiment further validates that GC‐induced activation of GR increases the binding of P300/cAMP response element‐binding protein (CBP) to the promoter region of constitutive androstane receptor (CAR), which leads to sustained H3K9 and H3K27 acetylation at the CAR locus, indirectly promoting CYP expression in adult offspring. Conclusively, the GR‐CAR pathway may play a pivotal role in programming CYP3A alteration in offspring exposed to elevated intrauterine GCs. This study provides novel insights into individual variations of CYPs expression and metabolic patterns.

SMAD3 gene methylation profile and asthma in childhood: A longitudinal approach.

ADHD-like behaviors in adolescent mice prenatally exposed to levetiracetam: No safe gestational dose across sexes.

Abstract Background Electromagnetic radiation (EMR) exposure has been linked to oxidative stress and neurochemical imbalances, potentially compromising cellular integrity. By increasing free radical production, EMR disrupts the antioxidant defense system, including glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT); which may contribute to neuronal damage and cognitive impairment. Method This study examines the impact of intrauterine mobile phone radiation (MPR) exposure on hippocampal neurotransmitters and oxidative stress markers in albino mice and their offspring. Thirty-five healthy mice, obtained from pregnant females aged 10–14 weeks (weighing 18–20 g), were randomly divided into seven groups (n = 5 per group), Group I (control, no MPR exposure); Groups II–IV (exposed to 2G 0.9 GHz, 3G 1.5 GHz, and 4G 1.95 GHz MPR until parturition, respectively); and Groups V–VII (exposed to the same frequencies until weaning). Results After eight weeks of exposure, hippocampal tissues were analyzed for neurochemical markers (acetylcholinesterase (AChE) and glutamate (GLU)) as well as oxidative stress biomarkers (malondialdehyde (MDA), SOD, and GSH) and their histological structure. MPR exposure resulted in a significant reduction ( p &lt; 0.05) in AChE levels in groups III–VII, except for group II ( p &gt; 0.05), while GLU levels significantly increased ( p &lt; 0.05) in group VII. Oxidative stress analysis revealed significantly elevated MDA and SOD levels ( p &lt; 0.05) and a marked reduction in GSH levels across all exposed groups ( p &lt; 0.05). Conclusion Intrauterine exposure to MPR induces oxidative stress and neurochemical imbalances in albino mice, which is characterized by decreased AChE and GSH levels and increased MDA, SOD, and GLU concentrations. These findings suggest that prolonged MPR exposure may disrupt hippocampal function, potentially affecting cognitive and neurodevelopmental processes.

BackgroundFetal hepatic glycogen is essential for intrauterine development and postnatal metabolic adaptation. This study aimed to explore the impact of intrauterine exposure to angiotensin II type 1 receptor autoantibodies (AT1-AA) on fetal hepatic glycogen homeostasis and underlying mechanisms.MethodsAT1-AA-positive pregnant rat models were established by intravenous administration of AT1-AA on gestational days 13 and 15, with angiotensin II- and L-NAME-treated groups serving as controls. Serum levels of AT1-AA in pregnant rats were quantified using ELISA. Fetal hepatic glycogen content was evaluated through PAS staining and an anthrone-sulfuric acid assay kit. On gestational day 18, fetal livers were harvested for RNA sequencing. Alterations in signaling molecules in hepatocytes were analyzed by Western blot.ResultsUnlike the angiotensin II- and L-NAME-treated groups, which similarly induced placental ischemia and growth restriction, intrauterine exposure of AT1-AA uniquely reduced fetal hepatic glycogen content at gestational day 18. This reduction was attributed to impaired glycogen synthesis, as characterized by decreased GYS2 expression and glycogen synthase activity. Transcriptomic profiling revealed that suppression of the PI3K/AKT pathway was the predominant mechanism involved. Both in vivo and in vitro studies confirmed that AT1-AA-mediated PI3K/AKT inhibition occurs through AT1R activation. Either stimulation of the PI3K/AKT pathway or blockade of AT1R significantly restored glycogen synthesis.ConclusionsOur study identifies AT1-AA as a unique maternal factor that selectively impairs fetal hepatic glycogen storage via AT1R-mediated suppression of PI3K/AKT pathway.

Background/Objectives: Overweight and obesity during pregnancy are metabolic risk factors that may compromise offspring brain development. The first 1000 days of life represent a critical window in which neurodevelopmental trajectories are shaped by intrauterine and early-life exposures. The 6- and 12-month milestones are key checkpoints where deviations may emerge, and interventions are most effective. This study evaluated the association between maternal pregestational weight status and infant neurodevelopment at 6 and 12 months of age. Methods: Mother and infant pairs from the OBESO perinatal cohort in Mexico City were included. Women in the first trimester of pregnancy were classified as normal weight and overweight/obesity according to their pregestational body mass index (pBMI), calculated from self-reported pre-pregnancy weight. Infant neurodevelopment was assessed at 6 and 12 months using the Bayley Scales of Infant Development III, Third Edition (BSID-III). Descriptive, bivariate and multiple linear regression analyses with mixed effects correction were conducted. Results: Among 97 mother–infant pairs, infants of mothers with overweight/obesity had lower language and socio-emotional scores at 12 months. Higher maternal pBMI was correlated with lower motor scores at 6 and 12 months, and with lower language scores at 12 months. Longitudinal analysis showed that maternal overweight/obesity was associated with a significant decline in language development from 6 to 12 months. (p = 0.002). Conclusions: Maternal pregestational overweight or obesity may negatively influence early neurodevelopment, particularly affecting language and cognitive domains during the first year of life. These early deficits could reflect alterations in intrauterine programming associated with maternal metabolic status.

Hearing assesment in children after intrauterine exposure to platinum-based treatment of pregnant cancer patients: A study from the International Network on Cancer, Infertility and Pregnancy

Lifelong impact of BPA: Steroidogenic reprogramming in aged gerbil adrenal glands following developmental exposure.